tbuckley/cabot-search huggingface dataset:
Redox Modulatory Cu(II)‐Baicalein Microflowers Prepared in One Step Effectively Promote Therapeutic Angiogenesis in Diabetic Mice
Authors: Kaijing Liu, Limei Liu, Haoyang Guo, Rong Xu, Xiaoyu Liang, Youlu Chen, Huiyang Li, Xue Fu, Xiaoli Wang, Houzao Chen, Yongjun Li, Jing Yang
Journal: Advanced Healthcare Materials (2022)

Abstract Reactive oxygen species (ROS) have been implicated in multiple cellular processes, and an imbalance in redox homeostasis gives rise to diseases, therefore, reestablishing redox homeostasis is a way to cure. Here, copper‐based metal‐organic networks (Cu‐MON) are generated by one‐step reaction using anti‐inflammatory and antioxidant baicalein as organic ligand and pro‐angiogenic copper as metal ions. Phosphate buffered saline is required for triggering Cu‐MON formation, and baicalein regulates the morphology and particle size of Cu‐MON. Cu‐MON are composed of Cu‐baicalein complexes (82.08 wt%) and Cu 3 (PO 4 ) 2 ·3H 2 O (17.92 wt%), thus exhibit a variable catalase‐like activity against different H 2 O 2 levels due to the reversible change between Cu 2+ /Cu 1+ /Cu 0 species. Intramuscular injection of Cu‐MON significantly increases blood flow of ischemic limb in diabetic mice, enhances the relative activities of redox‐related enzymes in ischemic muscle, thus effectively ameliorating the oxidative damage. Taken together, through moderate and dynamic “precise homeostasis regulation of cells,” Cu‐MON can be an efficient therapeutic strategy for peripheral arterial disease with diabetic complications.
More healthcare consumption is not the answer to our ailments
Authors: Mohammad S Razai, Pippa Oakeshott
Journal: BMJ (2022)

More healthcare consumption is not the answer to our ailments Mohammad S Razai, Pippa OakeshottMillions of patients are waiting to access care in a system under immense strain.Long waits can lead to poorer outcomes and exacerbate the suffering of those seeking treatment, something that we should not overlook.However, we must also acknowledge that more healthcare does not necessarily mean better health.It is increasingly evident that medical overuse can have detrimental effects on health and wellbeing.
Corrigendum to: EGFR, the Lazarus target for precision oncology in glioblastoma
Authors: Benjamin Lin, Julia Ziebro, Erin Smithberger, Kasey R Skinner, Eva Zhao, Timothy F Cloughesy, Zev A Binder, Donald M O’Rourke, David A Nathanson, Frank B Furnari, C Ryan Miller
Journal: Neuro-Oncology (2022)

48 was erroneously omitted after the sentence: "Deletion variants, EGFRvII and EGFRvIII, and assorted EGFR missense variants, EGFRG63R, EGFRR108K, EGFRA289V, and EGFRG598V structurally converge to constitutively expose this cryptic epitope by removing steric hinderance in the N-TR1 fragment."This error has been corrected.
Bioethics Consultation and First-Order Moral Reasoning: Leaving Philosophy at the Hospital Doors
Authors: Dave Langlois, Jeremy Butler
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article refers to:The Place of Philosophy in Bioethics Today Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Does cardiovascular preparticipation screening cause psychological distress in athletes? A systematic review
Authors: Braeden Hill, Nicholas Grubic, Matthew Williamson, Dermot M Phelan, Aaron L Baggish, Paul Dorian, Jonathan A Drezner, Amer M Johri
Journal: British Journal of Sports Medicine (2022)

Objective To evaluate the psychological implications of cardiovascular preparticipation screening (PPS) in athletes. Design Systematic review. Data sources MEDLINE, EMBASE, PubMed, CINAHL, SPORTDiscus, APA PsycInfo, Cochrane Library and grey literature sources. Study eligibility criteria Observational and experimental studies assessing a population of athletes who participated in a cardiovascular PPS protocol, where psychological outcomes before, during and/or after PPS were reported. Methods Results of included studies were synthesised by consolidating similar study-reported measures for key psychological outcomes before, during and/or after screening. Summary measures (medians, ranges) were computed across studies for each psychological outcome. Results A total of eight studies were included in this review (median sample size: 479). Study cohorts consisted of high school, collegiate, professional and recreational athletes (medians: 59% male, 20.5 years). Most athletes reported positive reactions to screening and would recommend it to others (range 88%–100%, five studies). Increased psychological distress was mainly reported among athletes detected with pathological cardiac conditions and true-positive screening results. In comparison, athletes with false-positive screening results still reported an increased feeling of safety while participating in sport and were satisfied with PPS. A universal conclusion across all studies was that most athletes did not experience psychological distress before, during or after PPS, regardless of the screening modality used or accuracy of results. Conclusion Psychological distress associated with PPS in athletes is rare and limited to athletes with true-positive findings. To mitigate downstream consequences in athletes who experience psychological distress, appropriate interventions and resources should be accessible prior to the screening procedure. PROSPERO registration number CRD42021272887.
CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
Authors: Sarah M. Larson, Christopher M. Walthers, Brenda Ji, Sanaz N. Ghafouri, Jacob Naparstek, Jacqueline Trent, Jia Ming Chen, Mobina Roshandell, Caitlin Harris, Mobina Khericha, Thomas Schweppe, Beata Berent-Maoz, Stanley B. Gosliner, Amr Almaktari, Melanie Ayala Ceja, Martin S. Allen-Auerbach, Jonathan Said, Karla Nawaly, Monica Mead, Sven de Vos, Patricia A. Young, Caspian Oliai, Gary J. Schiller, John M. Timmerman, Antoni Ribas, Yvonne Y. Chen
Journal: Cancer Discovery (2022)

To address antigen escape and loss of T-cell functionality, we report a phase I clinical trial (NCT04007029) evaluating autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR; CART19/20) for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), with safety as the primary endpoint. Ten patients were treated with 36 × 106 to 165 × 106 CART19/20 cells. No patient experienced neurotoxicity of any grade or over grade 1 cytokine release syndrome. One case of dose-limiting toxicity (persistent cytopenia) was observed. Nine of 10 patients achieved objective response [90% overall response rate (ORR)], with seven achieving complete remission [70% complete responses (CR) rate]. One patient relapsed after 18 months in CR but returned to CR after receiving a second dose of CART19/20 cells. Median progression-free survival was 18 months and median overall survival was not reached with a 17-month median follow-up. In conclusion, CART19/20 TN/MEM cells are safe and effective in patients with relapsed/refractory NHL, with durable responses achieved at low dosage levels. Autologous CD19/CD20 bispecific CAR-T cell therapy generated from TN/MEM cells for patients with NHL is safe (no neurotoxicity, maximum grade 1 cytokine release syndrome) and demonstrates strong efficacy (90% ORR, 70% CR rate) in a first-in-human, phase I dose-escalation trial. This article is highlighted in the In This Issue feature, p. 517.
Effect of the COVID-19 Pandemic on Place of Death Among Medicaid and Commercially Insured Patients With Cancer in Washington State
Authors: Laura E. Panattoni, Cara L. McDermott, Li Li, Qin Sun, Catherine R. Fedorenko, Hayley A. Sanchez, Karma L. Kreizenbeck, Veena Shankaran, Scott D. Ramsey
Journal: Journal of Clinical Oncology (2022)

PURPOSE The COVID-19 pandemic–related disruptions in health care delivery might have affected end-of-life care in patients with cancer. We examined changes in place of death and hospice support for Medicaid and commercially insured patients during the pandemic. PATIENTS AND METHODS We linked Washington State cancer registry records with claims from Medicaid and two commercial insurers for patients with solid tumor age 18-64 years. The study included 322 Medicaid and 162 commercial patients who died between March 2017 and June 2019 (pre–COVID-19), along with 90 Medicaid and 47 commercial patients who died between March and June 2020 (COVID-19). Place of death was categorized as hospital, hospice (home or nonhospital facility), and home without hospice. Place of death was compared using adjusted multinomial logistic regressions stratified by payer and time period (pre–COVID-19 v COVID-19). The clinical and sociodemographic factors associated with dying at home without hospice were examined, and adjusted marginal effects (ME) are reported. RESULTS In the adjusted pre–COVID-19 analysis, Medicaid patients were more likely than commercially insured patients to die in hospital (48% v 36%; adjusted ME, 11%; P = .02). In the pre–COVID-19/COVID-19 analysis, Medicaid patients' place of death shifted from hospital (48% v 32%; ME, −16%; P &lt; .01) to home without hospice (19.9% v 38.0%; ME, 16.5%; P &lt; .01). However, there were no statistically significant changes pre–COVID-19/COVID-19 for commercial patients. As a result, during COVID-19, Medicaid patients were more likely than commercial patients to die at home without hospice (38% v 22%; ME, 16%; P = .04) as were male versus female patients (ME, 16%; P &lt; .01). CONCLUSION The pandemic might have disproportionately worsened the end-of-life experience for Medicaid enrollees with cancer. Attention should be paid to societal and health system factors that decrease access to care for Medicaid patients.
Transplantation of neural stem progenitor cells from different sources for severe spinal cord injury repair in rat
Authors: Bai Xu, Man Yin, Yaming Yang, Yunlong Zou, Wenbin Liu, Lianyong Qiao, Jixiang Zhang, Zhan Wang, Yayu Wu, He Shen, Minghan Sun, Weiyuan Liu, Weiwei Xue, Yongheng Fan, Qi Zhang, Bing Chen, Xianming Wu, Ya Shi, Falong Lu, Yannan Zhao, Zhifeng Xiao, Jianwu Dai
Journal: Bioactive Materials (2022)

Neural stem progenitor cell (NSPC) transplantation has been regarded as a promising therapeutic method for spinal cord injury (SCI) repair. However, different NSPCs may have different therapeutic effects, and it is therefore important to identify the optimal NSPC type. In our study, we compared the transcriptomes of human fetal brain-derived NSPCs (BNSPCs), spinal cord-derived NSPCs (SCNSPCs) and H9 embryonic stem-cell derived NSPCs (H9-NSPCs) in vitro and subsequently we transplanted each NSPC type on a collagen scaffold into a T8-9 complete SCI rat model in vivo. In vitro data showed that SCNSPCs had more highly expressed genes involved in nerve-related functions than the other two cell types. In vivo, compared with BNSPCs and H9-NSPCs, SCNSPCs exhibited the best therapeutic effects; in fact, SCNSPCs facilitated electrophysiological and hindlimb functional recovery. This study demonstrates that SCNSPCs may be an appropriate candidate cell type for SCI repair, which is of great clinical significance.
Response to botulinum toxin may predict response to peroral pyloromyotomy in patients with gastroparesis
Authors: Vaibhav Wadhwa, Adalberto Gonzalez, Francisco Azar, Harjinder Singh, Kapil Gupta, Hong Liang, Alison Schneider, Jeffery Ponsky, Tolga Erim, John Rodriguez, Fernando J. Castro
Journal: Endoscopy (2022)

BACKGROUND : Patients with gastroparesis who have undergone prior intrapyloric botulinum toxin injection (BTI) may seek an opinion regarding peroral pyloromyotomy (POP). There are only two small reports assessing the role of BTI as a predictor for successful treatment with POP.We performed a retrospective cohort study to assess whether symptomatic improvement after BTI predicts a response to POP. We included 119 patients who had undergone both BTI and POP at Cleveland Clinic Ohio or Cleveland Clinic Florida from January 2016 to September 2019.65.5 % of patients had symptomatic improvement after BTI. Gastroparesis Cardinal Symptom Index (GCSI) scores were available for 74 patients, with 64 % achieving a response to POP, defined as a decrease in mean GCSI ≥ 1. In multivariable analysis, response to BTI (odds ratio [OR] 7.7 [95 %CI 2.2-26.1]) and higher pre-POP GCSI score (OR 2.3 [95 %CI 1.2-4.6]) were independent predictors of response to POP.Clinical improvement after BTI is a predictor of response to POP in patients with gastroparesis. This information may aid in improving patient selection for POP.
Circulating c-Met–Expressing Memory T Cells Define Cardiac Autoimmunity
Authors: Silvia Fanti, Edward Stephenson, Etel Rocha-Vieira, Alexandros Protonotarios, Stavroula Kanoni, Eriomina Shahaj, M. Paula Longhi, Vishal S. Vyas, Carlene Dyer, Elena Pontarini, Angeliki Asimaki, Carlos Bueno-Beti, Monica De Gaspari, Stefania Rizzo, Cristina Basso, Michele Bombardieri, David Coe, Guosu Wang, Daniel Harding, Iain Gallagher, Egle Solito, Perry Elliott, Stephane Heymans, Maurits Sikking, Konstantinos Savvatis, Saidi A. Mohiddin, Federica M. Marelli-Berg
Journal: Circulation (2022)

Autoimmunity is increasingly recognized as a key contributing factor in heart muscle diseases. The functional features of cardiac autoimmunity in humans remain undefined because of the challenge of studying immune responses in situ. We previously described a subset of c-mesenchymal epithelial transition factor (c-Met)-expressing (c-Met+) memory T lymphocytes that preferentially migrate to cardiac tissue in mice and humans. In-depth phenotyping of peripheral blood T cells, including c-Met+ T cells, was undertaken in groups of patients with inflammatory and noninflammatory cardiomyopathies, patients with noncardiac autoimmunity, and healthy controls. Validation studies were carried out using human cardiac tissue and in an experimental model of cardiac inflammation. We show that c-Met+ T cells are selectively increased in the circulation and in the myocardium of patients with inflammatory cardiomyopathies. The phenotype and function of c-Met+ T cells are distinct from those of c-Met-negative (c-Met-) T cells, including preferential proliferation to cardiac myosin and coproduction of multiple cytokines (interleukin-4, interleukin-17, and interleukin-22). Furthermore, circulating c-Met+ T cell subpopulations in different heart muscle diseases identify distinct and overlapping mechanisms of heart inflammation. In experimental autoimmune myocarditis, elevations in autoantigen-specific c-Met+ T cells in peripheral blood mark the loss of immune tolerance to the heart. Disease development can be halted by pharmacologic c-Met inhibition, indicating a causative role for c-Met+ T cells. Our study demonstrates that the detection of circulating c-Met+ T cells may have use in the diagnosis and monitoring of adaptive cardiac inflammation and definition of new targets for therapeutic intervention when cardiac autoimmunity causes or contributes to progressive cardiac injury.
Systematic review of arts and culture-based interventions for people living with dementia and their caregivers
Authors: Pilar A. Letrondo, Sarah A. Ashley, Andrew Flinn, Alexandra Burton, Thomas Kador, Naaheed Mukadam
Journal: Ageing Research Reviews (2022)

To explore and summarize studies investigating the effect of arts and culture interventions for people living with dementia and their caregivers on the well-being and cognition of the person living with dementia and, caregiver strain.We carried out a systematic search of five electronic databases (PubMed, PsychINFO, Embase, CINAHL, and Cochrane Library). We included original research published in peer-reviewed journals including both qualitative and quantitative studies. We assessed quality of included studies using the Cochrane Collaboration's Risk of Bias tools. A narrative synthesis was conducted of all included studies.Of the 4827 articles screened, 34 articles met inclusion criteria. A variety of interventions were identified, with more than half taking place in a museum or gallery. Five RCTs showed improvements in wellbeing outcomes but no cognitive improvements except in some subscales in a music intervention. Most non-randomised studies reported cognitive improvements and well-being improvements for people living with dementia and their caregivers. Studies primarily focused on individuals with mild to moderate dementia.The use of arts and culture interventions may provide benefits for people living with dementia and their caregivers. However, heterogeneity of the interventions and outcome measures prevented generalization of the results. Further research of arts and culture interventions for people living with dementia and their caregivers should utilize larger controlled trials, standardized outcome measures and include individuals with moderate to severe dementia.
Targeting the CD47/thrombospondin-1 signaling axis regulates immune cell bioenergetics in the tumor microenvironment to potentiate antitumor immune response
Authors: Elizabeth R Stirling, Masaki Terabe, Adam S Wilson, Mitra Kooshki, Liliya M Yamaleyeva, Martha A Alexander-Miller, Wei Zhang, Lance D Miller, Pierre L Triozzi, David R Soto-Pantoja
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background CD47 is an integral membrane protein that alters adaptive immunosurveillance when bound to the matricellular glycoprotein thrombospondin-1 (TSP1). We examined the impact of the CD47/TSP1 signaling axis on melanoma patient response to anti-PD-1 therapy due to alterations in T cell activation, proliferation, effector function, and bioenergetics. Methods A syngeneic B16 mouse melanoma model was performed to determine if targeting CD47 as monotherapy or in combination with anti-PD-1 impacted tumor burden. Cytotoxic (CD8+) T cells from Pmel-1 transgenic mice were used for T cell activation, cytotoxic T lymphocyte, and cellular bioenergetic assays. Single-cell RNA-sequencing, ELISA, and flow cytometry was performed on peripheral blood mononuclear cells and plasma of melanoma patients receiving anti-PD-1 therapy to examine CD47/TSP1 expression. Results Human malignant melanoma tissue had increased CD47 and TSP1 expression within the tumor microenvironment compared with benign tissue. Due to the negative implications CD47/TSP1 can have on antitumor immune responses, we targeted CD47 in a melanoma model and observed a decrease in tumor burden due to increased tumor oxygen saturation and granzyme B secreting CD8+ T cells compared with wild-type tumors. Additionally, Pmel-1 CD8+ T cells exposed to TSP1 had reduced activation, proliferation, and effector function against B16 melanoma cells. Targeting CD47 allowed CD8+ T cells to overcome this TSP1 interaction to sustain these functions. TSP1 exposed CD8+ T cells have a decreased rate of glycolysis; however, targeting CD47 restored glycolysis when CD8+ T cells were exposed to TSP1, suggesting CD47 mediated metabolic reprogramming of T cells. Additionally, non-responding patients to anti-PD-1 therapy had increased T cells expressing CD47 and circulating levels of TSP1 compared with responding patients. Since CD47/TSP1 signaling axis negatively impacts CD8+ T cells and non-responding patients to anti-PD-1 therapy have increased CD47/TSP1 expression, we targeted CD47 in combination with anti-PD-1 in a melanoma model. Targeting CD47 in combination with anti-PD-1 treatment further decreased tumor burden compared with monotherapy and control. Conclusion CD47/TSP1 expression could serve as a marker to predict patient response to immune checkpoint blockade treatment, and targeting this pathway may preserve T cell activation, proliferation, effector function, and bioenergetics to reduce tumor burden as a monotherapy or in combination with anti-PD-1.
Arizona’s debt collection reform—a small step towards health justice
Authors: Christopher Robertson, Steffie Woolhandler, David U Himmelstein
Journal: BMJ (2022)

A new law will protect people in Arizona from some of the harshest consequences of medical debt. Yet the policies of individual states can’t substitute for the US implementing a more humane system of universal health insurance coverage, say <b>David U Himmelstein and colleagues</b>
Myelofibrosis
Authors: Francesco Passamonti, Barbara Mora
Journal: Blood (2022)

The clinical phenotype of primary and post-polycythemia vera and postessential thrombocythemia myelofibrosis (MF) is dominated by splenomegaly, symptomatology, a variety of blood cell alterations, and a tendency to develop vascular complications and blast phase. Diagnosis requires assessing complete cell blood counts, bone marrow morphology, deep genetic evaluations, and disease history. Driver molecular events consist of JAK2V617F, CALR, and MPL mutations, whereas about 8% to 10% of MF are "triple-negative." Additional myeloid-gene variants are described in roughly 80% of patients. Currently available clinical-based and integrated clinical/molecular-based scoring systems predict the survival of patients with MF and are applied for conventional treatment decision-making, indication to stem cell transplant (SCT) and allocation in clinical trials. Standard treatment consists of anemia-oriented therapies, hydroxyurea, and JAK inhibitors such as ruxolitinib, fedratinib, and pacritinib. Overall, spleen volume reduction of 35% or greater at week 24 can be achieved by 42% of ruxolitinib-, 47% of fedratinib-, 19% of pacritinib-, and 27% of momelotinib-treated patients. Now, it is time to move towards new paradigms for evaluating efficacy like disease modification, that we intend as a robust and unequivocal effect on disease biology and/or on patient survival. The growing number of clinical trials potentially pave the way for new strategies in patients with MF. Translational studies of some molecules showed an early effect on bone marrow fibrosis and on variant allele frequencies of myeloid genes. SCT is still the only curative option, however, it is associated with relevant challenges. This review focuses on the diagnosis, prognostication, and treatment of MF.
CD47-SIRPα axis blockade in NASH promotes necroptotic hepatocyte clearance by liver macrophages and decreases hepatic fibrosis
Authors: Hongxue Shi, Xiaobo Wang, Fang Li, Brennan D. Gerlach, Arif Yurdagul, Mary P. Moore, Sharon Zeldin, Hanrui Zhang, Bishuang Cai, Ze Zheng, Luca Valenti, Ira Tabas
Journal: Science Translational Medicine (2022)

Necroptosis contributes to hepatocyte death in nonalcoholic steatohepatitis (NASH), but the fate and roles of necroptotic hepatocytes (necHCs) in NASH remain unknown. We show here that the accumulation of necHCs in human and mouse NASH liver is associated with an up-regulation of the “don’t-eat-me” ligand CD47 on necHCs, but not on apoptotic hepatocytes, and an increase in the CD47 receptor SIRPα on liver macrophages, consistent with impaired macrophage-mediated clearance of necHCs. In vitro, necHC clearance by primary liver macrophages was enhanced by treatment with either anti-CD47 or anti-SIRPα. In a proof-of-concept mouse model of inducible hepatocyte necroptosis, anti-CD47 antibody treatment increased necHC uptake by liver macrophages and inhibited markers of hepatic stellate cell (HSC) activation, which is responsible for liver fibrogenesis. Treatment of two mouse models of diet-induced NASH with anti-CD47, anti-SIRPα, or AAV8-H1-shCD47 to silence CD47 in hepatocytes increased the uptake of necHC by liver macrophages and decreased markers of HSC activation and liver fibrosis. Anti-SIRPα treatment avoided the adverse effect of anemia found in anti-CD47–treated mice. These findings provide evidence that impaired clearance of necHCs by liver macrophages due to CD47-SIRPα up-regulation contributes to fibrotic NASH, and suggest therapeutic blockade of the CD47-SIRPα axis as a strategy to decrease the accumulation of necHCs in NASH liver and dampen the progression of hepatic fibrosis.